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Tumor Burden Monitoring with Circulating Tumor DNA During Treatment in Patients with Esophageal Squamous Cell Carcinoma

  • Thoracic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

To guide appropriate treatment strategy, an accurate tumor monitoring modality that reflects tumor burden during neoadjuvant treatment is required for esophageal squamous cell carcinoma (ESCC). We aimed to investigate the clinical utility of circulating tumor DNA (ctDNA) in plasma in patients who received neoadjuvant chemotherapy (NAC) followed by esophagectomy.

Patients and Methods

Longitudinally collected plasma samples for ctDNA combined with genomic DNA from primary lesions were obtained from patients with histologically confirmed ESCC who underwent NAC followed by subtotal esophagectomy. Next-generation sequencing was performed to identify mutations from the plasma and the primary tumor. The relationships between changes in ctDNA and the pathological response and recurrence were assessed in patients with locally advanced ESCC.

Results

In pretreatment samples from 13 patients, multiple concordant mutations in ctDNA and primary tumors were observed in 11 patients (85%), who were classified as ctDNA positive before treatment. The ctDNA positive rate after NAC correlated with the pathological response (responders, 25%; nonresponders, 100%; p = 0.007). The risk of recurrence increased significantly in patients with positive ctDNA after surgery in analysis of 16 patients; the 1-year recurrence-free survival rates were 90 and 0% in ctDNA-negative and ctDNA-positive groups, respectively (p = 0.0008). In two patients with postoperative recurrence, ctDNA was detected approximately 5.5 months earlier than the diagnosis using radiographical imaging.

Conclusions

ctDNA is a promising biomarker for predicting pathological response and postoperative recurrence in ESCC. To demonstrate the external validity, we are currently preparing a multicenter prospective study.

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Acknowledgment

The authors would like to thank Hiroshi Yamada and Emmy Yanagita, technicians at the Genomics units at Keio University School of Medicine, for their technical assistance in preparing the NGS library and sequencing; Michiru Sugimoto, a technician at the Department of Surgery in Keio University School of Medicine, for her help with the laboratory experiments; and Kumiko Motooka, a staff member at the Department of Surgery in Keio University School of Medicine, for her help in the manuscript preparation.

Funding

The authors received no financial support for the research, authorship, or publication of this article.

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Authors and Affiliations

  1. Department of Surgery, Keio University School of Medicine, Tokyo, Japan

    Yosuke Morimoto MD, Satoru Matsuda MD, PhD, Hirofumi Kawakubo MD, PhD, Ryota Kobayashi MD, Kazuhiko Hisaoka MD, Jun Okui MD, MPH, Masashi Takeuchi MD, PhD, Kazumasa Fukuda PhD, Rieko Nakamura MD, PhD & Yuko Kitagawa MD, PhD

  2. Genomics Unit, Keio Cancer Center, Keio University School of Medicine, Tokyo, Japan

    Kohei Nakamura MD, PhD, Eriko Aimono MD & Hiroshi Nishihara MD, PhD

  3. Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan

    Jun Okui MD, MPH

  4. Cancer Center, Fujita Health University, Aichi, Japan

    Hideyuki Saya MD, PhD

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  1. Yosuke Morimoto MD
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Corresponding author

Correspondence to Satoru Matsuda MD, PhD.

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Disclosure

Author Yuko Kitagawa is Editor in Chief of Annals of Gastroenterological Surgery and author Satoru Matsuda is Editor of Annals of Gastroenterological Surgery. Authors Yosuke Morimoto, Satoru Matsuda, Hirofumi Kawakubo, Kohei Nakamura, Ryota Kobayashi, Kazuhiko Hisaoka, Jun Okui, Masashi Takeuchi, Eriko Aimono, Kazumasa Fukuda, Rieko Nakamura, Hideyuki Saya, and Hiroshi Nishihara have no conflicts of interest or financial ties to disclose. Author Yuko Kitagawa reports grants from Chugai Pharmaceutical Co. Ltd.; Taiho Pharmaceutical Co. Ltd.; Yakult Honsha Co. Ltd.; Asahi Kasei Pharma Corporation; Otsuka Pharmaceutical Co., Ltd.; Takeda Pharmaceutical Co., Ltd.; Ono Pharmaceutical Co. Ltd.; Tsumura & Co.; Kyowa Hakkou Kirin Co., Ltd.; EA Pharma Co., Ltd.; Medicon Inc.; Kaken Pharmaceutical Co. Ltd.; Eisai Co., Ltd.; Otsuka Pharmaceutical Factory Inc.; Teijin Pharma Limited; Nihon Pharmaceutical Co. Ltd.; and Nippon Covidien Inc.; and personal fees from Asahi Kasei Pharma Corporation; AstraZeneca K.K.; Ethicon Inc.; Ono Pharmaceutical Co. Ltd.; Otsuka Pharmaceutical Factory, Inc.; Olympus Corporation; Nippon Covidien Inc.; Shionogi & Co. Ltd.; Taiho Pharmaceutical Co. Ltd.; Chugai Pharmaceutical Co. Ltd.; Bristol-Myers Squibb K.K.; MSD K.K.; Smith & Nephew KK; Kaken Pharmaceutical Co. Ltd.; and ASKA Pharmaceutical Co., Ltd. outside the submitted work.

Ethical Approval

Patients were recruited in accordance with the Declaration of Helsinki, and this study was approved by the Institutional Review Board of Keio University School of Medicine (IRB no. 20190057). Written informed consent was obtained from all patients.

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Morimoto, Y., Matsuda, S., Kawakubo, H. et al. Tumor Burden Monitoring with Circulating Tumor DNA During Treatment in Patients with Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 30, 3747–3756 (2023). https://doi.org/10.1245/s10434-023-13194-z

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